Late measures of microstructural alterations in severe neonatal hypoxic–ischemic encephalopathy by MR diffusion tensor imaging

Neonatal hypoxic–ischemic encephalopathy is a major cause of brain damage in infants, and is associated with periventricular white matter injury and chronic neurological dysfunctions. However, the mechanisms of the chronic white matter injury and reorganization are still unclear. In this study, in vivo diffusion tensor imaging (DTI) was employed to evaluate the late changes of white matter microstructural integrity in the rat brains at 10 weeks after severe neonatal hypoxic–ischemic insults at postnatal day 7. In the fractional anisotropy directionality map, qualitative evaluation showed that a dorsoventrally oriented fiber bundle extended from the corpus callosum into the cyst in the anterior brain, whilst the posterior peri-infarct areas had similar fiber orientations as the contralateral internal capsule, optic tract and fimbria of hippocampus. Compared to the contralateral hemisphere, significantly higher fractional anisotropy, axial diffusivity and diffusion trace value were observed quantitatively in the distal end of the extended fiber bundle connecting the anterior and posterior white matters rostrocaudally. A significantly lower fractional anisotropy but higher axial and radial diffusivities and trace were also found in the ipsilateral corpus callosum, proximal external capsule and anterior commissure, while slightly lower fractional anisotropy and axial diffusivity were noticed in the ipsilateral internal capsule and optic nerve. It was suggested that increased fractional anisotropy, axial diffusivity and trace characterize white matter reorganization in chronic neonatal hypoxic–ischemic insults, whereas reduction in fractional anisotropy appears to characterize two types of white matter lesions, with significantly higher axial and radial diffusivities and trace being primary and slightly lower axial diffusivity being secondary. Combined with fractional anisotropy directionality map, in vivo DTI provides important indices to differentiate the chronic effects of severe neonatal hypoxic–ischemic injury and recovery globally, quantitatively and non-invasively.     

The Combination of the Gastrointestinal Integrin (α4β7) and Selectin Ligand Enhances T-Cell Migration to the Reproductive Tract During Infection with Chlamydia trachomatis

Problem  Chlamydia trachomatis causes sexually transmitted infection and reproductive dysfunction worldwide. Identifying a population of endocervical T-cells to target in vaccine development is likely to enhance efficacy of a vaccine and reduce reproductive tract dysfunction.
Method of study  Endocervical samples were obtained from young women and flow cytometric analysis was used to identify lymphocytes that appeared in the genital tract in response to sexually transmitted bacterial infections caused by C. trachomatis.
Results  Increased numbers of α4β7+CLA+ memory T-cells, a unique T-cell phenotype, were found in the endocervix of human female subjects infected with C. trachomatis .
Conclusion A unique population of memory T lymphocytes expressing both α4β7 and CLA gain access to reproductive tract tissues during a sexually transmitted infection with C. trachomatis and should be considered in development of vaccines against sexually transmitted infections.     

Versatility of Hemisternotomy for Cardiac Surgery

Abstract   Background: Hemisternotomy has been suggested as a way to reduce morbidity by limiting the invasiveness of surgical interventions but it is often limited to aortic valve disease. This study reviews the experience of one center employing hemisternotomy and compares patient outcomes, both in-hospital and post-discharge, with a matched group of full sternotomy patients. Methods: Propensity scores were used to match all hemisternotomy valve cases (Hemi) to full sternotomy valve cases (Full) (1:2). An in-hospital composite outcome (COMP) was defined as mortality, stroke, deep sternal wound infection, sepsis, or return to operating room (OR) for bleeding or valve dysfunction. Provincial administrative health databases were used to determine freedom from mortality and hospital readmission for cardiac cause. Results: During the study period, 70 patients received hemisternotomy for various cardiac surgical interventions with only 38 patients undergoing isolated aortic valve replacement. Examining valve surgery exclusively, 65 Hemi were matched to 130 Full. In-hospital complications were low in both groups, with 1.0% mortality and a non-significant trend toward COMP in the Full group (Hemi = 4.6%; Full = 8.5%; p = 0.39). Ventilation time was significantly decreased in Hemi (median four vs. six hours; p = 0.002). At two years follow-up, survival was excellent for both (Hemi = 95.0%; Full = 93.6%) and freedom from cardiac morbidity (Hemi = 76.8%, Full = 73.2%) was comparable. Conclusion: Hemisternotomy appears to be a safe, effective, and versatile alternative for many cardiac surgical interventions. With a median follow-up of four years, this study represents the longest cardiac morbidity follow-up for hemisternotomy patients. However, we were unable to conclusively show a morbidity benefit with this incision.     

Corticosterone reduces dendritic complexity in developing hippocampal CA1 neurons

Although prolonged stress and corticosteroid exposure induce morphological changes in the hippocampal CA3 area, the adult CA1 area is quite resistant to such changes. Here we addressed the question whether elevated corticosteroid hormone levels change dendritic complexity in young, developing CA1 cells. In organotypic cultures (prepared from P5 rats) that were 14–21 days cultured in vitro, two doses of corticosterone (30 and 100 nM) were tested. Dendritic morphology of CA1 neurons was established by imaging neurons filled with the fluorescent dye Alexa. Application of 100 nM corticosterone for 20 minutes induced atrophy of the apical dendritic tree 1–4 hours later. Fractal analysis showed that total neuronal complexity was reduced twofold when compared with vehicle‐treated neurons. Exposing organotypic slices to 30 nM corticosterone reduced apical length in a more delayed manner: only neurons examined more than 2 hours after exposure to corticosterone showed atrophy of the apical dendritic tree. Neither dose of corticosterone affected the length of basal dendrites or spine density. Corticosterone was ineffective in changing morphology of the apical dendrites when tested in the presence of the glucocorticoid receptor antagonist RU38486. These results suggest that high physiological levels of corticosterone, via activation of the glucocorticoid receptor, can, during the course of only a few hours, reduce the dendritic complexity of CA1 pyramidal neurons in young, developing hippocampal tissue. These findings suggest that it is relevant to maintain plasma corticosterone levels low during hippocampal development. © 2009 Wiley‐Liss, Inc.     

Getting it right: designing adolescent-centred smoking cessation services

Aims To demonstrate the importance of identifying adolescent preferences for smoking cessation in order to inform the design of effective adolescent cessation services. Design Structured qualitative interviews drawing on means‐end theory. Setting Three youth‐clubs and two secondary schools in south‐east Wales. Participants Twenty‐five male and female 13–18‐year‐olds, mainly daily smokers. Findings Interviewees did not assume immediately that a smoking cessation service is something that will be available to them, and therefore they initially encountered difficulties in identifying attributes of such support. With further prompting interviewees were able to express a preference for support attributes, but these were not attributes that traditionally form part of cessation provision. Their main preference was for support from friends and family, access to nicotine replacement therapy and non‐school‐based, flexible support and guidance. Conclusion The results re‐emphasize the inadequacies of existing cessation provision for meeting adolescent preferences and suggest that developing more adolescent‐appropriate support requires a reconceptualization of existing interventions, with service users situated at the core of intervention design. The study highlights a number of service development points for intervention planners including: rethinking the timing and location of provision; placing more emphasis on the selection of facilitators; harnessing support from friends and family; and rooting these developments in broader tobacco control strategies.     

Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs

PURPOSE: A biotechnologic breakthrough for the study of drug permeability across the blood-brain barrier (BBB) would be the use of a reproducible in vitro model that recapitulates the functional, structural, and pathologic properties of the BBB in situ. We developed a humanized dynamic in vitro BBB model (DIV-BBB) based on cocultures of human microvascular endothelial cells (HBMECs) from "normal" and drug-resistant epileptic brain tissue with human brain astrocytes (HAs) from epilepsy patients or controls. METHODS: HBMECs and HAs were cocultured for 28 days in polypropylene capillaries. HBMECs were exposed to physiologic levels of shear stress generated by intraluminal flow. Permeability to [3H]sucrose, [14C]phenytoin, and [14C]diazepam was measured in control and drug-resistant DIV-BBB with and without pretreatment with the MDR1 inhibitor XR9576. BBB integrity was monitored by transendothelial electrical resistance measurements (TEERs). Cell growth and viability were assessed by measurement of glucose consumption and lactate production. RESULTS: PSucrose and TEER values did not depend on the origin of the endothelium used (epileptic or normal). PPhenytoin was 10-fold less (1.54 x 10(-6) cm/s) in drug-resistant BBB models than in controls (1.74 x 10(-5) cm/s). MDR1 blockade with XR9576 was effective (3.5-fold increase) only in drug-resistant cultures. PDiazepam in control and drug-resistant DIV-BBB was not affected by XR9576 and did not depend on the epileptic or control origin of endothelia. The overall contribution of epileptic glia to pharmacoresistance was negligible. CONCLUSIONS: These results show that, for the substances used, the humanized DIV-BBB recapitulates the physiologic permeability properties of the BBB in vivo and is also capable of mimicking a drug-resistant BBB phenotype.     

Stereotypy in young children with autism and typically developing children

Although stereotypy is one of the key diagnostic features of autism, few studies have compared stereotypic behavior in children with autism and typically developing children. The present study employed direct observational measurement methods to assess levels of stereotypic behavior in 2-, 3- and 4-year-old children with autism or pervasive developmental disorder - not otherwise specified (PDD-NOS) and age-matched typically developing peers. Thirty children with autism or PDD-NOS and 30 typically developing children participated. Each child's performance of several early learning and play skills was assessed using a direct observational assessment protocol developed for children with autism who were entering early intensive behavioral treatment. Duration of episodes of vocal and motor stereotypy was recorded from a videotaped 10 min portion of that assessment session. Results indicated that the 2-year-old children with autism or PDD-NOS had somewhat higher levels of stereotypic behavior than the typically developing 2-year-olds, while the 3- and 4-year-old children with autism or PDD-NOS displayed substantially higher levels stereotypic behavior than their same-age peers.     

The Latino Mental Health Project: A Local Mental Health Needs Assessment

In this article, we present the results of a local needs assessment of the mental health experiences, service needs, and barriers to treatment-seeking of the Latino population in Worcester, Massachusetts. Overall, participants reported relatively high rates of experiences with symptoms of mental health problems, they indicated using a range of both formal and alternative mental health services, and they noted a variety of instrumental, attitudinal, and culturally-specific barriers to seeking mental health services. Findings are discussed with regards to the role that community-driven research can play in advancing efforts to provide relevant services to underserved populations. Preparation of this article was supported by a grant from the Blue Cross Blue Shield of Massachusetts Foundation to the Massachusetts Department of Mental Health with Sara Adams as the project director, and a National Institute of Mental Health (NIMH) Career Development Award K01 MH67571 to Esteban Cardemil.